ArticleACS omega2024
Binding Mechanism of the Active Form of Molnupiravir to RdRp of SARS-CoV-2 and Designing Potential Analogues: Insights from Molecular Dynamics Simulations.
Article in ACS omega, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Positive-Strand RNA Viral RdRps: From Structure Conservation and Activity Assay to Drug Development.Molecules (Basel, Switzerland) · 2026Review
- Design, Synthesis and Biological Exploration of NovelInternational journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molnupiravir, an FDA-approved nucleoside prodrug for treating COVID-19, converts into N4-hydroxycytidine triphosphate (NHC-TP), which integrates into SARS-CoV-2 RNA by its RNA-dependent RNA polymerase (RdRp) causing lethal mutations in viral proteins. Due to the risk of RdRp-mediated drug resistance and potential off-target effects on host polymerases (e.g., human polymerase II/HPolII), it is crucial to understand NHC-TP interactions at polymerase active sites for developing new, resistance-proof treatments. In this study, we used molecular dynamics (MD) simulations to probe key interactions between NHC-TP and SARS-CoV-2 RdRp and designed novel NHC-TP analogues with greater selectivity for SARS-CoV-2 RdRp over HPolII by a virtual screening workflow. We docked NHC-TP to a modified SARS-CoV-2 RdRp-Remdesivir triphosphate structure (PDB ID: 7BV2) and generated 71 NHC-TP analogues with bulky substituents to increase the interaction with RdRP and to reduce HPolII incorporation. MD simulations assessed the stability, binding affinity, and site interactions of these analogues. The top 7 candidates, with favorable ADMET properties, likely inhibit replication via potential dual mechanisms (the replicative stalling and the induction of lethal mutations) while maintaining selectivity for SARS-CoV-2 RdRp.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.